Bilayer vesicles or liposomes whose walls comprise monomeric lipids, such as phosphatidyl cholines, have been studied as drug carriers, offering the attractive properties of promoting passage of the drugs across cell membranes, increasing drug lifetime in the plasma and retarding drug catabolism. Liposomes formed from monomeric phosphatidyl cholines are, however, thermodynamically and biologically unstable and the rate of leakage of entrapped drugs from them is relatively high. Consequently, their practical utility for such purposes may be limited.
More recently, the concept of polymerized vesicles, formed from polymerizable material has been proposed (Regen et al., J. Am. Chem. Soc. 1980, 102, 6638) as a method of achieving enhanced stability. Vesicles of this type are also disclosed in U.S. patent application Ser. No. 618,634 filed June 8, 1984 as a division of Ser. No. 382,296 filed May 26, 1982 which was a continuation-in-part of Ser. No. 280,633 filed July 6, 1981. Biological studies conducted to date on such polymerized vesicles, such as vesicles derived from bis[12-(methacryloyloxy)dodecanoyl]-L-alpha-phosphatidyl-choline, indicate that they do not induce platlet aggregation to any appreciable degree and can be administered in substantial amounts, intravenously, without any evidence of acute toxicity, as indicated by survival, kidney function and liver function. However, chronic parenteral use of these as well as all other previously reported polymerized phosphatidylcholine vesicles may result in tissue accumulation of the nondegradable polymeric backbones.
U.S. Pat. No. 4,348,329 discloses conjugated di-yne containing phospholipids which may be polymerized and/or crosslinked, but not reversibly so.
Thus, the use of polymerized vesicles for the controlled, in vivo delivery of medicaments may require, in some cases, the need for vesicles that, in one way or another, could be safely removed or prevented from accumulating, as such.
An object of the present invention therefore, is to provide a novel class of monomeric materials from which polymerized biodegradable vesicles may be prepared.
A further object of the present invention is to provide polymeric biodegradable vesicles.
A further object of the present invention is to provide a novel class of polymeric vesicles which will provide a polymerized liposome network which may be readily depolymerized.